Amine neurotransmitters and their metabolites are studied in blood, cerebrospinal fluid (CSF), and urine to assess neurochemical alterations which may be associated with clinical diagnoses, clinical states, particular behavioral or psychopathological dimensions, or treatment with drugs. Because of both methodological advances in assays for low concentrations of metabolites and problems associated with the probenecid technique, CSF studies have focussed increasingly on baseline (non-probenecid) lumbar punctures. During the past year sources of variance in urinary MHPG have been addressed in several methodological studies. Previously-reported diagnostic group differences and state-related changes in urinary MHPG have been confirmed. A variety of personality and behavioral variables have been associated with specific CSF and urinary metabolites. Drug response prediction studies based on pre-treatment metabolite levels continue. The completed desmethylimipramine/zimelidine crossover trial demonstrates specific in vivo CSF metabolite changes corresponding to in vitro effects on reuptake (i.e., the noradrenergic tricyclic selectively decreases CSF MHPG, while the serotonergic tetracyclic selectively decreases CSF 5-HIAA); however, both agents decrease urinary MHPG raising further questions about the meaning of the urinary measure.